Abstract：
:Poverty, displacement, and parental stress represent potent sources of early life stress (ELS). Stress disproportionately affects females, who are at increased risk for stress-related pathologies associated with cognitive impairment. Mechanisms underlying stress-associated cognitive impairment and enhanced risk of females remain unknown. Here, ELS is associated with impaired rule-reversal (RR) learning in females, but not males. Impaired performance was associated with decreased expression and density of interneurons expressing parvalbumin (PV+) in orbitofrontal cortex (OFC), but not other interneuron subtypes. Optogenetic silencing of PV+ interneuron activity in OFC of control mice phenocopied RR learning deficits observed in ELS females. Localization of reversal learning deficits to PV+ interneurons in OFC was confirmed by optogenetic studies in which neurons in medial prefrontal cortex (mPFC) were silenced and associated with select deficits in rule-shift learning. Sex-, cell-, and region-specific effects show altered PV+ interneuron development can be a driver of sex differences in cognitive dysfunction.
journal_name
Cell Repjournal_title
Cell reportsauthors
Goodwill HL,Manzano-Nieves G,LaChance P,Teramoto S,Lin S,Lopez C,Stevenson RJ,Theyel BB,Moore CI,Connors BW,Bath KGdoi
10.1016/j.celrep.2018.11.010subject
Has Abstractpub_date
2018-11-27 00:00:00pages
2299-2307.e4issue
9issn
2211-1247pii
S2211-1247(18)31756-Xjournal_volume
25pub_type
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